Mesothelin is a cell surface protein that is highly expressed in aggressive cancers such as malignant mesothelioma, ovarian cancer, pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma, bile duct carcinoma and gastric cancer. As a result, mesothelin is an excellent candidate for tumor targeted immunotherapeutics. However, the antibodies against mesothelin that are available for clinical trials are of murine origin. These antibodies have the potential to elicit immune responses in patients, which may adversely affect the ability to provide patients with repeated doses. Thus, the clinical application of the antibodies may be limited.
In order to address the issue of immunogenicity in patients, NIH inventors have generated anti-mesothelin antibody variable fragments (Fv) of human origin. These antibody fragments (HN1 and HN2) have the ability to efficiently recognize mesothelin on the surface of numerous cancer cells. As a result, these antibody fragments represent an attractive therapeutic alternative to the murine anti-mesothelin antibodies currently being tested in clinical trials.